1. Introduction to General Pathology and Pathophysiology. Role in the biomedical disciplines - State of health and disease status - Homeostasis as balance between opposing actions - The state of health as a point of equilibrium - The method: way ahead - General etiology: genetic, epigenetic and environmental causes of disease - Terminology issues in medicine and dentistry - The global burden of diseases - Main causes of death and disease in developed countries towards developing countries - Concept of pathogenesis - Competition between diseases and life expectancy at birth.
2. Cellular pathology. Cell damage and death. Causes of cell damage. Morphological alterations in cell damage: reversible damage, necrosis. Cell damage mechanisms: ATP depletion, mitochondrial damage, intracellular calcium entry and loss of calcium homeostasis, accumulation of reactive species and free oxygen radicals, membrane permeability defects, DNA and protein damage. Ischemic and hypoxic damage. Chemical damage. Apoptosis: causes of apoptosis, morphological and biochemical changes in apoptosis, mechanisms of apoptosis, apoptosis in physiological and pathological conditions. Autophagy. Intracellular accumulations. Pathological calcification. Cell aging.
3. Genetic diseases. Architecture and functions of the human genome. Mutations. Epigenetic alterations. Mendelian diseases. Complex multigene diseases. Chromosomal alterations and chromosomal diseases. Diseases with atypical monogenic heredity. Molecular diagnosis of genetic and epigenetic diseases.
4. Acute and chronic inflammation. NFkB, self and non-self recognition. Background. Acute inflammation: stimuli of acute inflammation, reaction of blood vessels in acute inflammation, reaction of leucocytes in inflammation, extinction of acute inflammatory response. Inflammation mediators: cell-derived mediators, mediators derived from plasma proteins. Outcomes of acute inflammation. Morphological aspects. Chronic inflammation: Causes, morphological characteristics and cellular responses. Granulomatous inflammation. Systemic effects and consequences. Fever.
5. Renewal, regeneration and tissue repair. Control of proliferation and tissue homeostasis: proliferative activity of tissues, stem cells and their role in tissue homeostasis. Growth factors and proliferative and anti-proliferative signals. The "checkpoints" of the cell cycle. Regeneration mechanisms of tissues and organs. Extracellular matrix and cell-matrix interactions. Healing for repair, scarring and fibrosis: angiogenesis, healing of skin wounds, local and systemic factors that affect wound healing, pathological aspects of wound healing, fibrosis.
6. Tissue adaptations to damage. Hyperplasia and physiological and pathological hypertrophy. Atrophy, aplasia and hypoplasia. Metaplasia. Dysplasia.
7. Neoplastic diseases. Molecular basis of cell transformation. Oncogenes, antioncogenes: their role in the mechanisms that control neoplastic transformation. Viral and cellular oncogenes: homologies and differences. MicroRNAs and tumors. Metabolic factors and Warburg effect in cell transformation. "Sporadic" and hereditary tumors. Examples of autosomal dominant syndromes. Benign and malignant tumors. General histogenetic classification. Oral and nasopharyngeal tumors: characteristics and risk factors. Molecular mechanisms involved in invasion and metastasis: general concepts. Primitive and metastatic tumors. Stages of metastatisation. Staging concepts. Elements of epidemiology of tumors. Immunity and tumors. Antigens and tumor markers. Elements of cancer therapy. Environmental and chemical carcinogenesis. Concepts of initiation and tumor promotion. Main direct and indirect chemical carcinogens. Carcinogenesis from ultraviolet and ionizing radiation. Tobacco and cancer. Viral carcerogenesis. Transformation induced by oncogenic viruses to DNA and RNA. Retroviruses, acute and chronic transformers. Oncogenic viruses in human tumors: papilloma virus, herpesvirus, hepatitic viruses, HTLV1 and HIV.
8. Infectious diseases. Parasitism, infection, infestation, intoxication. Evolutionary adaptations in the host-micro-organism pathogen relations. Socio-cultural and environmental factors involved in the origin and spread of infectious diseases. Transmission routes of infectious agents. Arthropod vectors. Mechanisms and barriers of natural defense and cellular and tissue pathogen response in different external and internal surfaces. Immunization. Virulence factors. Eso and endotoxins. Endotoxic shock: definition, risk factors and pathogenetic mechanisms. Bacterial infectious diseases. Chronic granulomatous infections. Syphilis, tuberculosis, leprosy. Rickettsial and chlamydial infections. Viruses as a cause of illness. Damage mechanisms. Major viral infections. Critical periods for infectious-fetal infectious damage. Herpesvirus infections. Main fungal infections. Main protozoal diseases.Outline of helminth diseases (main nematode infestations, trematodes, cestodes) Overview of ectoparasitic arthropods. The so-called prion diseases. Molecular pathophysiology of prion infections. Prion concept and history of discovery. Exogenous, endogenous and hereditary prion diseases.
9. Hemodynamic diseases, atherosclerosis, thromboembolic disease and shock. Edema, haemorrhage, hemostasis and thrombosis. Coagulation mechanisms and their alterations. Atherosclerosis: characteristics and pathogenetic mechanisms. Thrombosis. Embolism. Heart attack. Shock.
10. Environmental and nutritional disorders. Diabetes. Obesity. Metabolic syndrome. Damage from physical and mechanical causes. Radiation. Acute and chronic damage from exciting radiations. Acute and chronic damage from ionizing radiation. Other radiation of the electromagnetic spectrum. Freezing. Burns. Trauma.
20. Introduction to the immune system. General properties and components of the immune system
21. Innate immunity. Recognition of microorganisms by innate immunity. Components of innate immunity. Avoidance of innate immunity by microorganisms. Role of innate immunity in the activation of adaptive immunity.
22. Capture and presentation of the antigen to lymphocytes. Characteristics of antigens recognized by T lymphocytes. Capture of protein antigens by antigen presenting cells. Major histocompatibility complex. Processing of protein antigens. Characteristics of the antigens recognized by B lymphocytes
23. Recognition of the antigen by adaptive immunity. Receptors for lymphocyte antigen. Development of immunological specificity.
24. Cell-mediated immune response. Recognition and costimulation of the antigen. Biochemical transduction pathways in T lymphocyte activation. Functional responses of T lymphocytes to antigens and costimulatory molecules.
25. Effective mechanisms of cell-mediated immunity. Cell-mediated responses. Migration of the effector T lymphocytes to the site of infection. Effector functions of T helper CD4 + lymphocytes. Effector functions of cytotoxic T CD8 + lymphocytes. Resistance of pathogenic mechanisms to cell-mediated immunity.
26. Humoral immune response. Activation of B lymphocytes by the antigen. Role of CD4 + helper T cells in the humoral response. Antibody response to T-independent antigens. Regulation of the humoral immune response: antibody feedback.
27. Effective mechanisms of humoral immunity. Properties and effector functions of antibodies. Neutralization of microorganisms and microbial toxins. Reactions mediated by eosinophils and mast cells. Opsonization and phagocytosis mediated by antibodies. Antibody-dependent cell cytotoxicity. Activation of the complement system. Antibody functions in particular anatomical sites. Avoidance of humoral immunity by microbes.
28. Tolerance and autoimmunity. Tolerance of lymphocytes T. Tolerance of lymphocytes B. Autoimmunity principles and pathogenesis. genetic factors of autoimmunity. Role of infections in autoimmunity.
29. Immunity against transplants. Immune responses against transplants.
30. Hypersensitivity. Hypersensitivity reactions. diseases caused by antibodies and immune complexes. Diseases caused by T lymphocytes
31. Congenital and acquired immunodeficiencies. Primary congenital immunodeficiencies. Secondary congenital immunodeficiencies. Acquired immunodeficiency syndrome.